Installation of Trimethyllysine Analogs on Intact Histones via Cysteine Alkylation

Bas J. G. E. Pieters, Jordi C. J. Hintzen, Yvonne Grobben, Abbas H. K. Al Temimi, Jos J. A. G. Kamps, Jasmin Mecinović*

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Resumé

Site-specific incorporation of post-translationally modified amino acids into proteins, including histones, has been a subject of great interest for chemical and biochemical communities. Here, we describe a site-specific incorporation of structurally simplest trimethyllysine analogs into position 4 of the intact histone H3 protein. An efficient alkylation of cysteine 4 of the recombinantly expressed histone H3 provides a panel of trimethyllysine analogs that differ in charge, charge density, sterics, and chain length. We demonstrate that H3 histone that bears trimethyllysine analogs can be further assembled into the octameric histone complex that constitutes the nucleosome. Binding studies showed that H3 histone that possesses trimethyllysine analogs is well recognized by a PHD3 reader domain of human JARID1A. This work provides important (bio)chemical tools for fundamental biomolecular studies aimed at unravelling the molecular basis of the higher order nucleosome and chromatin assemblies.

OriginalsprogEngelsk
TidsskriftBioconjugate Chemistry
Vol/bind30
Udgave nummer3
Sider (fra-til)952-958
ISSN1043-1802
DOI
StatusUdgivet - 2019

Fingeraftryk

Alkylation
Histones
Cysteine
Proteins
Charge density
Chain length
Amino acids
Nucleosomes
Chromatin Assembly and Disassembly
Chromatin
trimethyllysine
Amino Acids

Citer dette

Pieters, Bas J. G. E. ; Hintzen, Jordi C. J. ; Grobben, Yvonne ; Temimi, Abbas H. K. Al ; Kamps, Jos J. A. G. ; Mecinović, Jasmin. / Installation of Trimethyllysine Analogs on Intact Histones via Cysteine Alkylation. I: Bioconjugate Chemistry. 2019 ; Bind 30, Nr. 3. s. 952-958.
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title = "Installation of Trimethyllysine Analogs on Intact Histones via Cysteine Alkylation",
abstract = "Site-specific incorporation of post-translationally modified amino acids into proteins, including histones, has been a subject of great interest for chemical and biochemical communities. Here, we describe a site-specific incorporation of structurally simplest trimethyllysine analogs into position 4 of the intact histone H3 protein. An efficient alkylation of cysteine 4 of the recombinantly expressed histone H3 provides a panel of trimethyllysine analogs that differ in charge, charge density, sterics, and chain length. We demonstrate that H3 histone that bears trimethyllysine analogs can be further assembled into the octameric histone complex that constitutes the nucleosome. Binding studies showed that H3 histone that possesses trimethyllysine analogs is well recognized by a PHD3 reader domain of human JARID1A. This work provides important (bio)chemical tools for fundamental biomolecular studies aimed at unravelling the molecular basis of the higher order nucleosome and chromatin assemblies.",
author = "Pieters, {Bas J. G. E.} and Hintzen, {Jordi C. J.} and Yvonne Grobben and Temimi, {Abbas H. K. Al} and Kamps, {Jos J. A. G.} and Jasmin Mecinović",
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Installation of Trimethyllysine Analogs on Intact Histones via Cysteine Alkylation. / Pieters, Bas J. G. E.; Hintzen, Jordi C. J.; Grobben, Yvonne; Temimi, Abbas H. K. Al; Kamps, Jos J. A. G.; Mecinović, Jasmin.

I: Bioconjugate Chemistry, Bind 30, Nr. 3, 2019, s. 952-958.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Installation of Trimethyllysine Analogs on Intact Histones via Cysteine Alkylation

AU - Pieters, Bas J. G. E.

AU - Hintzen, Jordi C. J.

AU - Grobben, Yvonne

AU - Temimi, Abbas H. K. Al

AU - Kamps, Jos J. A. G.

AU - Mecinović, Jasmin

PY - 2019

Y1 - 2019

N2 - Site-specific incorporation of post-translationally modified amino acids into proteins, including histones, has been a subject of great interest for chemical and biochemical communities. Here, we describe a site-specific incorporation of structurally simplest trimethyllysine analogs into position 4 of the intact histone H3 protein. An efficient alkylation of cysteine 4 of the recombinantly expressed histone H3 provides a panel of trimethyllysine analogs that differ in charge, charge density, sterics, and chain length. We demonstrate that H3 histone that bears trimethyllysine analogs can be further assembled into the octameric histone complex that constitutes the nucleosome. Binding studies showed that H3 histone that possesses trimethyllysine analogs is well recognized by a PHD3 reader domain of human JARID1A. This work provides important (bio)chemical tools for fundamental biomolecular studies aimed at unravelling the molecular basis of the higher order nucleosome and chromatin assemblies.

AB - Site-specific incorporation of post-translationally modified amino acids into proteins, including histones, has been a subject of great interest for chemical and biochemical communities. Here, we describe a site-specific incorporation of structurally simplest trimethyllysine analogs into position 4 of the intact histone H3 protein. An efficient alkylation of cysteine 4 of the recombinantly expressed histone H3 provides a panel of trimethyllysine analogs that differ in charge, charge density, sterics, and chain length. We demonstrate that H3 histone that bears trimethyllysine analogs can be further assembled into the octameric histone complex that constitutes the nucleosome. Binding studies showed that H3 histone that possesses trimethyllysine analogs is well recognized by a PHD3 reader domain of human JARID1A. This work provides important (bio)chemical tools for fundamental biomolecular studies aimed at unravelling the molecular basis of the higher order nucleosome and chromatin assemblies.

U2 - 10.1021/acs.bioconjchem.9b00065

DO - 10.1021/acs.bioconjchem.9b00065

M3 - Journal article

C2 - 30794748

VL - 30

SP - 952

EP - 958

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 3

ER -